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Podcast Review: Big Unknowns – can we stop ageing?

16 January 2017
Appeared in BioNews 884

Big Unknowns – can we stop ageing?

The Guardian's Science Weekly, 29 November 2016

Presented by Nicola Davis

As you probably need no reminding, 2016 was a year of loss for many: deaths of beloved family, friends, artists, scientists, and any semblance of decency in political discourse. As the year drew to its bloody close, The Guardian's Science Weekly podcast questioned the inevitability of all this loss.

Staunchly attempting to blockade the march of time stands the resplendently bearded Dr Aubrey de Grey, a former computer scientist turned biomedical gerontologist, who spoke to podcast presenter Nicola Davis. Many researchers now think that ageing occurs due to the accumulation of damage at a molecular level; Dr de Grey's idea is that stopping ageing is a matter of repairing the damage the body does to itself.

Over the years, his lab has identified several types of damage. The first is when cells die and don't get replaced, as with degenerative diseases such as Parkinson's. The next is the damage that occurs through having too many cells, as with cancers or when cells don't die when they should. Over time, mutations accumulate in your mitochondria, the little power packs within each of your cells. Waste products also build up in cells, when they would normally be destroyed or excreted, while junk builds up outside cells.

The final form of damage is something called cross-linking. An extracellular matrix formed of proteins runs through your body, performing many different functions. Partly, it acts as a scaffold, but it also helps your cells communicate with one another, and helps with growing and healing. Dr de Grey described this matrix as a kind of elastic lattice that becomes stiffer with age. This stiffening – a result of cross-links between the extracellular molecules – can lead to conditions such as arteriosclerosis (hardening of the arteries).

According to Dr de Grey, cancers are the most difficult component of ageing to stop because tumours evolve by natural selection within your body. Biologist Dr Leslie Orgel once said: 'Evolution is cleverer than you are.' (Don't take it personally; I'm sure he meant all of us.) Natural selection allows tumours to adapt and evolve complex behaviours. This means that cancer is an especially wily foe.

While researchers like Dr de Grey look at how ageing happens by focussing on bodily mechanisms, others look into the reasons why evolution might allow ageing to exist in the first place.

One explanation for the 'why' of ageing, espoused by another guest on the show – Dr Justin Werfel from Harvard University – is that evolution favours genes that essentially program organisms to die. Dr Werfel creates simulations of evolution: computerised thought experiments about what is possible. One of his simulations has suggested that ageing and death might serve a function when organisms live in ecosystems where food and other resources are not evenly distributed. Dr Werfel found that, in these environments, immortal individuals can wind up overexploiting their environments, but the mortals – through their limited lifespans – do not. So, a gene for death can win out, evolutionarily speaking.

Unfortunately, that's not quite the be-all and end-all. In Dr Werfel's simulation, when organisms carrying the 'death gene' die, they turn into resources that other organisms can feast on, whereas the 'immortals' don't leave any resources behind. Since the organisms reproduce by converting the resources around them into offspring, those programmed to die can essentially move around their environment, while the immortal organisms are stuck in place. Ageing experts Dr Axel Kowald and Professor Tom Kirkwood noticed this quirk in their recent article about simulations of programmed death. When Dr Kowald and Professor Kirkwood extended Dr Werfel's simulation to allow organisms to move around regardless of whether or not they carried the gene for programmed death, it seemed that evolution favoured mobility, rather than favouring individuals programmed to die. (Full disclosure: I collaborated with Professor Kirkwood a few years ago.)

The third guest was Dr Jenny Tullet, a biogerontologist who looks at how roundworms grow old. Dr Tullet has found a gene that she calls the 'master regulator of ageing', which can increase or decrease its lifespan by switching other genes on and off. Dr Tullet made the important point that in 'our quest for longevity', we must also improve the amount of time that people are healthy, not simply allow a longer span in which to suffer. This chimes nicely (read: depressingly) with predictions about our ageing population – namely that, by 2040, one in 12 people will be over 80 years old, and there will be 37 pensioners for every 100 working-age people. Add to this the debates about climate change and overpopulation, and you find a bittersweet future ahead.

While superbly interesting, this episode presented the three lines of research rather uncritically. For example, there is a tension between Dr Werfel's view of evolutionarily programmed death and Dr de Grey's belief we can stop ageing by repairing the damage that occurs as a side effect of living. The former idea suggests that stopping ageing is a matter of finding and tweaking the genes that help damage to accumulate, implying that damage repair would be a fool's errand. On the other hand, if genes that favour ageing don't exist, we run the risk of a lot of misdirected effort. It would also have been good if the programme had tried to link Dr Tullet's research into the genetics of ageing with Dr de Grey's work on how ageing happens.

How to die well and how to cheat death will remain relevant topics. We need to get better not only at dying, but also at accepting that death will eventually become us all. We must come to terms with our limits as much as we attempt to push them. And, for all of Dr de Grey's incredible optimism about what we might achieve in the future, we still find ourselves in a world without Bowie.

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